Novel Intervention to Influence Muscle Plasticity in Veterans

Novel Intervention to Influence Muscle Plasticity in Veterans

Sponsors

Lead sponsor: VA Office of Research and Development

Collaborator: University of Iowa

Source VA Office of Research and Development
Brief Summary

The loss of muscle contraction (paralysis) removes an important stimulus for maintenance of overall health for individuals with complete spinal cord injury (SCI). Increased protein catabolism (atrophy) limits important stresses to the skeletal system. Bone loss doubles the risk of fracture and contributes to increased mortality in Veterans with SCI. Metabolic syndrome and diabetes lead to heart disease in Veterans with SCI at higher rates than the general population. Exercise methods to sustain muscle tissue, bone density, and metabolic stability after SCI are lacking scientific justification. If left unchecked, the secondary complications of SCI can be health limiting or even life threatening to Veterans with paralysis. The importance of maintaining the health of the musculoskeletal system after SCI has never been greater as a cure for paralysis may become a reality. Contemporary rehabilitation interventions lack the ability to functionally load muscle tissue, quantify the dose of load, stress the cardiovascular system, monitor the overall stresses during daily exercise training, or offer portability to improve compliance with the exercise. The long-term goal of this project is to establish the optimal dose of muscle and bone stress during functional exercise in order to improve the health of Veterans with complete paralysis. The practical outcome of this research is to offer a form of activity that is feasible, portable, and grounded in sound scientific principles. The scientific goal is to understand whether the dose of force generated in paralyzed muscle via evoked contractions is critical to muscle atrophy/hypertrophy molecular pathways, physiologic performance, and insulin sensitivity. The investigators will administer various doses of muscle force by manipulating the frequency of electrical stimulation while keeping stimulation current (i.e. muscle fiber recruitment) constant. Interestingly, no previous study has examined the dose of muscle force necessary to trigger adaptations in protein synthesis/degradation pathways. The investigators wish to discover the most effective method to maintain the molecular and physiologic properties of paralyzed muscle. The investigators believe such a method will be in urgent demand as a co-intervention with pharmaceutical strategies in post-SCI rehabilitation.

Detailed Description

Central Hypothesis: The investigators hypothesize that high muscle force induced via a novel, portable, active standing intervention will increase muscle force properties, alter gene expression for atrophy and fiber type pathways, and improve systemic insulin sensitivity in Veterans with complete paralysis.

Aim 1: To determine the training effects of 3 tiers of quadriceps muscle force on muscle physiological properties in Veterans with chronic paralysis from SCI.

Aim 2: To determine the training effects of 3 tiers of quadriceps muscle forces on muscle mRNA for genes associated with atrophy and muscle fiber type in Veterans with complete paralysis.

Aim 3: To determine the training effects of 2 tiers of compressive load induced by quadriceps muscle forces on insulin sensitivity and markers of inflammation in Veterans with SCI.

Overall Status Completed
Start Date April 2011
Completion Date December 2014
Primary Completion Date December 2014
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
HF Muscle Force up to 1 year
HF Muscle Force up to 1 year
HF Muscle Force up to 1 year
LF Muscle Force up to 1 year
LF Muscle Force up to 1 year
LF Muscle Force up to 1 year
Skeletal Muscle Gene Regulation: MSTN up to 1 year
Skeletal Muscle Gene Regulation: MSTN up to 1 year
Skeletal Muscle Gene Regulation: MSTN up to 1 year
Skeletal Muscle Gene Expression: PPARGC1A up to 1 year
Skeletal Muscle Gene Expression: PPARGC1A up to 1 year
Skeletal Muscle Gene Expression: PPARGC1A up to 1 year
Enrollment 33
Condition
Intervention

Intervention type: Behavioral

Intervention name: Low-force muscle stimulation

Description: Electrical stimulation of paralyzed muscle in seated or standing to evoke non-summated, low-force contractions, using either a lab-based system or a portable system for up to 1 year.

Arm group label: Arm 2: Low-force muscle stimulation

Intervention type: Behavioral

Intervention name: High-force muscle stimulation

Description: Electrical stimulation of paralyzed muscle in seated or standing to evoke summated, high-force contractions, using either a lab-based system or a portable system for up to 1 year.

Arm group label: Arm 1: High-force muscle stimulation

Intervention type: Behavioral

Intervention name: Sequential low-force and high-force muscle stimulation

Description: Electrical stimulation of paralyzed muscle in seated or standing to evoke non-summated, low-force contractions, followed by: 1) a 1-month washout period, then; 2) electrical stimulation to evoke summated, high-force contractions.

Arm group label: Arm 3: Sequential low-force and high-force muscle stimulation

Eligibility

Criteria:

Inclusion Criteria:

- Inclusion criteria for all subjects will be upper motor neuron lesions between the 10th thoracic and the 7th cervical spinal levels. The completeness of the injury will be verified by somatosensory evoked potentials.

Exclusion Criteria:

- Subjects will be excluded if they have pressure ulcers

- chronic infection

- lower extremity muscle contractures

- deep vein thrombosis

- recent limb fractures

- muscle metabolic disorders

- any comorbid disease known to affect bone metabolism (such as parathyroid dysfunction)

- or if they are pregnant or plan to become pregnant.

- Subjects with distal femur trabecular bone mineral density less than 50 mg/cm3 will be excluded from participation in quadriceps electrical stimulation training

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Richard K Shields, PhD PT Principal Investigator Iowa City VA Health Care System, Iowa City, IA
Location
facility
Iowa City VA Health Care System, Iowa City, IA
Location Countries

United States

Verification Date

February 2016

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Arm group label: Arm 1: High-force muscle stimulation

Arm group type: Experimental

Description: High-force muscle stimulation

Arm group label: Arm 2: Low-force muscle stimulation

Arm group type: Experimental

Description: Low-force muscle stimulation

Arm group label: Arm 3: Sequential low-force and high-force muscle stimulation

Arm group type: Experimental

Description: Sequential low-force and high-force muscle stimulation

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov